This invention relates to radiopaque polyurethane compositions having a bromine content of from 10 to 35% by weight prepared by the reaction of cycloaliphatic diisocyanates, certain polyester diols, and a sufficient amount of a bromine-containing aromatic chain extender to provide the required bromine content.
When medical or veterinary devices are inserted or implanted in a subject, it is often desirable to be able to locate them by X-ray examination, particularly when catheters or cannulas are being inserted into body cavities, passages, or vessels. It is also often desirable, especially with catheters, to observe visually fluids within exposed portions of such devices.
Consequently, an object of the present invention is to prepare radiopaque polyurethane compositions that are preferably optically transparent.
Several approaches for achieving this object in catheters have been reported. For example, U.S. Pat. No. 2,212,334 discloses the incorporation of short segments of radiopaque material within otherwise transparent tubes by introduction of such material at regular intervals during manufacture of the catheters. Alternatively, U.S. Pat. Nos. 2,857,915, 4,027,659, and 4,105,732 disclose the introduction of the radiopaque material as continuous stripes running the length of the catheters. It is also possible to include a radiopaque material only at the distal end of the catheter, as disclosed in U.S. Pat. No. 3,605,750, but the intervening portion of the catheter is not readily detectable by X-ray examination. Similarly, U.S. Pat. No. 3,529,633 discloses catheters made primarily from polymers that are opaque to both X-rays and visible light but also have small sections made from transparent materials.
Another variant of this approach is described in U.S. Pat. No. 3,618,614, which discloses a multiwall tubing having a thick transparent inner tube encased within a thin transparent tube containing a radiopaque material. In this variant, the relatively longer path-length through edges of the tube provides sufficient contrast to appear during X-ray examination. U.S. Pat. No. 3,336,918 discloses similar effects obtained by incorporating metal powders into polyurethane coatings.
Yet another approach is to disperse X-ray opaque substances, such as barium sulfate, a bismuth halide, or a halogen-containing plasticizer, diol, or other such halogen-containing material, throughout a visually transparent polymer. See, for example, Y. Delaviz et al., Polymer Preprints (Polymer Division, Am. Chem. Soc.), 30, 215-216 (1989), and U.S. Pat. Nos. 3,608,555, 3,645,955, 3,749,134, 3,901,829, and 4,282,876. Blends of polymers, at least one of which is radiopaque, are reported, for example, in U.S. Pat. No. 4,182,787, to provide similar effects. Each of these approaches, however, involves the use of physical blends, at least some of which have inherent disadvantages. For example, some of the radiopaque substances can be leached out of the polymeric substrate and absorbed by the body. In addition, some additives can have other incompatibilities that make them unsuitable for use in humans or animals.
It would be particularly advantageous to make the medical or veterinary devices from a polymeric material in which the radiopaque component is incorporated as a structural unit of the polymer. For example, U.S. Pat. No. 4,722,344, which is incorporated by reference, discloses polyurethanes prepared using halogenated polyols and/or halogenated polyisocyanates as reactants. Although the polyurethanes disclosed in U.S. Pat. No. 4,722,344 incorporate sufficient bromine to provide the desired radiopacity, these polyurethanes have a high flex modulus but do not exhibit the desirable softening effect in saline solutions (which are used in testing as a substitute for blood).
Optically transparent radiopaque polyurethanes that are dimensionally stable under standard sterilization conditions (for example, ethylene oxide treatment or gamma irradiation) would be desirable. This stability can be achieved by using crystalline building blocks. For example, polyester diols based on adipic acid and C.sub.4 -C.sub.8 alkanediols can provide elastomers having enhanced crystallinity. Aromatic chain extenders can further enhance polymer crystallinity. It is possible to make radiopaque polyurethanes based on cycloaliphatic diisocyanates, polyester diols, and isocyanate-reactive bromine-containing compounds, but polyester-polyurethanes of this type that are both radiopaque and optically transparent have not previously been reported.
Soft optically transparent radiopaque polyurethanes have been disclosed in U.S. Pat. No. 5,177,170 but the disclosed polyurethanes are based on polyethers and certain aliphatic bromine-containing chain extenders rather than on the polyester and/or polycarbonate polyols and aromatic bromine-containing chain extenders of the present invention.
It was, therefore, an object of the present invention to obtain radiopaque polyurethanes (preferably optically transparent polyurethanes) having high halogen content that are normally hard and elastic but which soften upon exposure to blood or saline solutions. This object has been accomplished by using polyols containing ester and/or carbonate groups and partially or completely replacing the previously reported brominated chain extenders with isocyanate-reactive bromine-containing aromatic chain extenders such as tetrabromobisphenol A bis(2-hydroxyethyl ether).